Molecular Imaging with PET to Measure Tumor Vascular Physiology in vivo in Man

PL06-02

Over the last 5 - 10 years the non invasive imaging of molecular interactions in man has become possible. In the emerging post genomic era molecular imaging provides an important tool for translating basic research into knowledge of the phenotype in vivo function and physiology. Molecular imaging can now move towards measuring gene expression in vivo, as well as DNA, RNA and protein interactions, mechanisms of action of drugs and tumour and normal tissue physiology. Positron emission tomography (PET) is the most sensitive and specific technology for in vivo molecular imaging in man.
 Tumour vascular physiology is a dynamic process and can be effectively studied in real time in man using PET. In this way we are now able to address essential mechanistic questions about in vivo tumour vasculature and response to anticancer therapy in man. Tumour vasculature is now an important target for therapy with several novel agents. Addressing the many mechanistic questions that have arisen with vasculature-targeted therapy would enable us to rationally exploit and improve cancer therapy. Changes in tumour vascular physiology are difficult to study in the patient. Molecular imaging with PET is ideally suited to tackle this, providing in vivo physiological measurements simultaneously in tumour and normal tissue. Oxygen 15 labelled water can be used to measure blood flow (with absolute quantitation in ml/mg/min) and volume of distribution (percentage of a tumour that is perfused). Angiogenesis itself can be explored using probes to the VEGF and other systems.
 PET studies have shown that vascular parameters are important in anticancer drug delivery. Higher tumour blood flow is associated with improved tumour exposure for both lipophilic and non-lipophilic drugs. The relationship between changes in tumour volume and tumour physiology in response to antiproliferative therapy has been shown to be complex. PET has been used to confirm the mechanism of action of vascular disruptive as well as antiangiogenic drugs in early clinical trials. Clinical trials indicate that certain antiangiogenic drugs increase chemosensitization. PET would allow the investigation of the mechanism of such sensitization in vivo in man, by assessing normalization of the tumour vasculature or augmenting the antivascular effects of chemotherapy via inhibition of the possible revascularisative stimulatory effect of circulating endothelial progenitor cells.
 This presentation will examine the relative merits of this technology, examples of its use and discuss the possibilities and potential for the future.